EP1212336B1 - Procede de preparation d'agglomerats spheriques de telithromycine et leur application dans la preparation de formes pharmaceutiques - Google Patents

Procede de preparation d'agglomerats spheriques de telithromycine et leur application dans la preparation de formes pharmaceutiques Download PDF

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Publication number
EP1212336B1
EP1212336B1 EP00958756A EP00958756A EP1212336B1 EP 1212336 B1 EP1212336 B1 EP 1212336B1 EP 00958756 A EP00958756 A EP 00958756A EP 00958756 A EP00958756 A EP 00958756A EP 1212336 B1 EP1212336 B1 EP 1212336B1
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EP
European Patent Office
Prior art keywords
telithromycin
preparation
spherical
production
agglomerates
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP00958756A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1212336A2 (fr
Inventor
Jean-Yves Godard
Valérie Rognon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aventis Pharma SA
Original Assignee
Aventis Pharma SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Application filed by Aventis Pharma SA filed Critical Aventis Pharma SA
Priority to SI200030287T priority Critical patent/SI1212336T1/sl
Publication of EP1212336A2 publication Critical patent/EP1212336A2/fr
Application granted granted Critical
Publication of EP1212336B1 publication Critical patent/EP1212336B1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the subject of the present invention is a method of preparation of spherical telithromycin agglomerates and their application in the preparation of pharmaceutical forms.
  • Telithromycin or 11,12-dideoxy-3-de ((2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl) oxy) -6-O-methyl-3-oxo -12,11- (oxycarbonyl ((4- (4- (3-pyridinyl) -1H-imidazol-1-yl) butyl) imino)) - erythromycin is a product with antibiotic structure properties: described and claimed in European patent 680967.
  • the oral route is a preferred form of administration for this product.
  • Telithromycin is an active ingredient that has a bad taste. We must therefore prepare dosage forms which mask the taste of the product and still retain a good bioavailability.
  • telithromycin The physico-chemical qualities of telithromycin are such that they allow micro-encapsulation, i.e. coating the active ingredient with a polymer or blend of polymers.
  • Micro-encapsulation can be carried out by spraying of a polymer or by interfacial polymerization or by coacervation.
  • a polymer or by interfacial polymerization or by coacervation.
  • the particles must be spherical so that the covering of the active ingredient by the polymer be correct and to get good kinetics of release of the active ingredient.
  • Spherical agglomerates are obtained by transformation direct spherical cluster crystals and the subject of the invention is therefore a method of preparation of spherical agglomerates characterized in that one prepares a suspension of telithromycin crystals, then coats these crystals of a phase insoluble in telithromycin which gradually crystallizes.
  • the subject of the invention is in particular a method of preparation characterized in that a solution is used of telithromycin in acetone.
  • the subject of the invention is more particularly a preparation process characterized in that the crystallization takes place in an acetone / ether mixture isopropyl.
  • the crystallization is carried out between -5 and -15 ° C.
  • the size of agglomerates spherical is controlled by adjusting the stirring speed.
  • the agglomerates according to the invention allow good microencapsulation and the subject of the invention is in particular the application characterized in that we surround the spherical agglomerates of a polymer layer to obtain the dosage form sought, for example microcapsules.
  • the spherical agglomerates of telithromycin obtained according to the invention are characterized in that the size of the particles is between 30 and 400 microns and in particular in that the median particle size is between 80 and 150 microns.
  • the spherical agglomerates of preferred telithromycin are characterized in that the size median of the particles is located around 100 microns, that is to say characterized in that half of the agglomerates have a size less than 100 microns.
  • Agitation is carried out under a slight nitrogen overpressure between 19 ° C. and 21 ° C and verifies that the dissolution is complete.
  • the temperature is stabilized between 19 ° and 21 ° C.
  • the mixture is stirred for 15 minutes at 20 ⁇ 1 ° C. and then the suspension at -10 ⁇ 1 ° C in 30 minutes.
  • the mixture is still stirred for 1 h at -10 ° C.
  • telithromycin 50.4 g of spherical agglomerates are obtained.
  • Particle size is determined by diffraction laser using a HELOS SYMPATEC® granulometer.
  • the product of the example was used to prepare by simple coacervation or by direct spraying of a suitable polymer for microcapsules intended for preparation of oral suspensions to be prepared immediately.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP00958756A 1999-08-26 2000-08-28 Procede de preparation d'agglomerats spheriques de telithromycine et leur application dans la preparation de formes pharmaceutiques Expired - Lifetime EP1212336B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
SI200030287T SI1212336T1 (sl) 1999-08-26 2000-08-28 Postopek za pripravo sferičnih algomeratov telitromicina in njihova uporaba pri pripravi farmacevtskih oblik

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9910810 1999-08-26
FR9910810A FR2797875B1 (fr) 1999-08-26 1999-08-26 Agglomerats spheriques de telithromycine, leur procede de preparation et leur application dans la preparation de formes pharmaceutiques
PCT/FR2000/002393 WO2001014393A2 (fr) 1999-08-26 2000-08-28 Agglomerats spheriques de telithromycine, leur procede de preparation et leur application dans la preparation de formes pharmaceutiques

Publications (2)

Publication Number Publication Date
EP1212336A2 EP1212336A2 (fr) 2002-06-12
EP1212336B1 true EP1212336B1 (fr) 2003-12-03

Family

ID=9549351

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00958756A Expired - Lifetime EP1212336B1 (fr) 1999-08-26 2000-08-28 Procede de preparation d'agglomerats spheriques de telithromycine et leur application dans la preparation de formes pharmaceutiques

Country Status (34)

Country Link
US (1) US6825218B1 (sl)
EP (1) EP1212336B1 (sl)
JP (1) JP4871467B2 (sl)
KR (1) KR100718222B1 (sl)
CN (1) CN1183151C (sl)
AR (1) AR025398A1 (sl)
AT (1) ATE255590T1 (sl)
AU (1) AU774385B2 (sl)
BR (1) BR0013569B1 (sl)
CA (1) CA2382497C (sl)
CO (1) CO5190666A1 (sl)
CZ (1) CZ2002594A3 (sl)
DE (1) DE60006976T2 (sl)
DK (1) DK1212336T3 (sl)
EA (1) EA005080B1 (sl)
ES (1) ES2209970T3 (sl)
FR (1) FR2797875B1 (sl)
HK (1) HK1049167B (sl)
HR (1) HRP20020167B1 (sl)
HU (1) HU229075B1 (sl)
IL (2) IL148128A0 (sl)
ME (2) MEP20108A (sl)
MX (1) MXPA02001988A (sl)
NO (1) NO322622B1 (sl)
PL (1) PL204100B1 (sl)
PT (1) PT1212336E (sl)
RS (1) RS50433B (sl)
SI (1) SI1212336T1 (sl)
SK (1) SK287588B6 (sl)
TR (1) TR200200506T2 (sl)
TW (1) TWI272949B (sl)
UA (1) UA73523C2 (sl)
WO (1) WO2001014393A2 (sl)
ZA (1) ZA200201599B (sl)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9902202D0 (sv) * 1999-06-10 1999-06-10 Astra Ab Production of aggregates
FR2821747B1 (fr) * 2001-03-09 2004-07-02 Ethypharm Lab Prod Ethiques Suspension de telithromycine a gout masque
US20040013737A1 (en) * 2002-07-19 2004-01-22 Philippe Becourt Taste masked oral composition of telithromycin
WO2004009059A1 (en) * 2002-07-19 2004-01-29 Aventis Pharma S.A. Taste masked oral composition of telithromycin
EP1524966B1 (en) * 2002-07-19 2009-11-25 Aventis Pharma S.A. Taste masked oral composition of telithromycin
EP1610878B1 (en) * 2003-02-21 2014-09-03 University Of Bath Process for the production of particles
WO2005007143A2 (en) * 2003-07-14 2005-01-27 The Board Of Trustees Of The University Of Illinois Use of makrolides and ketolides for the treatment of tuberculosis
WO2007039914A2 (en) * 2005-10-06 2007-04-12 Alembic Limited Novel polymorphs of telithromycin
US20090075917A1 (en) * 2007-09-19 2009-03-19 Protia, Llc Deuterium-enriched telithromycin
KR101324862B1 (ko) * 2011-07-12 2013-11-01 (주)에이에스텍 클로피도그렐 황산수소염의 구형 입자, 이를 포함하는 약학적 조성물 및 이의 제조방법

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE31635T1 (de) * 1983-06-22 1988-01-15 Univ Ohio State Res Found Herstellung von feinen materialien.
JPH02227130A (ja) * 1989-02-28 1990-09-10 Taisho Pharmaceut Co Ltd 球形微小凍結粒子の製造法
FR2719587B1 (fr) * 1994-05-03 1996-07-12 Roussel Uclaf Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments.

Also Published As

Publication number Publication date
HK1049167B (zh) 2005-08-19
CZ2002594A3 (cs) 2002-09-11
EP1212336A2 (fr) 2002-06-12
BR0013569A (pt) 2002-05-14
CA2382497C (fr) 2011-06-28
HK1049167A1 (en) 2003-05-02
FR2797875B1 (fr) 2001-10-19
PL353137A1 (en) 2003-10-20
CN1371386A (zh) 2002-09-25
DK1212336T3 (da) 2004-03-15
HRP20020167A2 (en) 2003-06-30
ES2209970T3 (es) 2004-07-01
ZA200201599B (en) 2003-04-30
PT1212336E (pt) 2004-04-30
WO2001014393A3 (fr) 2001-06-21
KR100718222B1 (ko) 2007-05-15
DE60006976T2 (de) 2004-10-21
HUP0202842A3 (en) 2003-03-28
KR20020033771A (ko) 2002-05-07
MEP20108A (en) 2010-06-10
AU774385B2 (en) 2004-06-24
PL204100B1 (pl) 2009-12-31
SI1212336T1 (sl) 2004-04-30
ME00112B (me) 2010-10-10
NO20020926D0 (no) 2002-02-26
SK287588B6 (sk) 2011-03-04
AU7018100A (en) 2001-03-19
CN1183151C (zh) 2005-01-05
EA005080B1 (ru) 2004-10-28
JP4871467B2 (ja) 2012-02-08
MXPA02001988A (es) 2002-08-20
RS50433B (sr) 2009-12-31
JP2003507484A (ja) 2003-02-25
HUP0202842A2 (hu) 2003-01-28
YU13202A (sh) 2004-09-03
EA200200294A1 (ru) 2002-08-29
TWI272949B (en) 2007-02-11
TR200200506T2 (tr) 2002-08-21
CA2382497A1 (fr) 2001-03-01
NO322622B1 (no) 2006-11-06
UA73523C2 (uk) 2005-08-15
CO5190666A1 (es) 2002-08-29
WO2001014393A2 (fr) 2001-03-01
AR025398A1 (es) 2002-11-27
IL148128A (en) 2006-10-31
SK2532002A3 (en) 2002-09-10
HRP20020167B1 (en) 2006-06-30
IL148128A0 (en) 2002-09-12
NO20020926L (no) 2002-02-26
US6825218B1 (en) 2004-11-30
DE60006976D1 (de) 2004-01-15
FR2797875A1 (fr) 2001-03-02
ATE255590T1 (de) 2003-12-15
BR0013569B1 (pt) 2014-02-25
HU229075B1 (hu) 2013-07-29

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